Localizing Medical Instruments Using Doppler Ultrasound Twinkling Artifact Signatures

ABSTRACT

Markers, medical instruments, and/or medical devices have a composition and/or other features or characteristics such that they will generate twinkling artifacts when imaged with ultrasound. In this way, the markers, medical instruments, and/or medical devices can be detected and localized using ultrasound. Ultrasound technical specifications that are optimized to generate twinkling artifact signatures are selected and used to facilitate localization of such markers, instruments, and/or devices.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of PCT/US2020/051844, filed on Sep. 21, 2020, and entitled “NON-METALLIC ULTRASOUND-DETECTABLE MARKERS,” which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/903,078, filed on Sep. 20, 2019, and entitled “NON-METALLIC ULTRASOUND-DETECTABLE MARKERS,” each of which are herein incorporated by reference in their entirety for all purposes.

BACKGROUND

Ultrasound (“US”)-guided radioactive seed localization of a treated pathology-proven metastatic axillary lymph node is the standard of care in sentinel lymph node surgery in patients with locally advanced metastatic breast cancer. Unfortunately, preoperative US-guided localization of the positive axillary lymph node associated with a metallic identifier or biopsy marker or clip can often be suboptimal or unsuccessful. The reasons for these detection failures are observed to be multifactorial and include poor sonographic conspicuity of the marker, as well as extrusion of the marker from the metastatic lymph node, which normalizes in size and morphology during neoadjuvant chemotherapy.

Thus, because numerous currently available metallic biopsy markers are difficult to visualize by ultrasound, there is an unmet clinical need for radiologists to be able to detect treatment site or biopsy markers by ultrasound, even several months after marker placement.

Kidney stones generate a so-called “twinkling artifact” or “color comet-tail artifact” when imaged with ultrasound; although, there is yet to be a consensus on the mechanism for this artifact. In the case of kidney stones, this twinkling artifact, is visible on color Doppler ultrasound examinations as a rapid alternation of color immediately behind the stationary echogenic stones, representing a false appearance of movement. These twinkling artifacts may also manifest when power Doppler and spectral Doppler scans are performed, where the twinkling artifacts appear as a sign of heterogeneous spectral expansion composed of adjacent vertical lines with no waveform.

SUMMARY OF THE DISCLOSURE

The present disclosure addresses the aforementioned drawbacks by providing a method for localizing an ultrasound-detectable marker. The method includes operating an ultrasound system to select imaging parameters, where the imaging parameters are selected to optimize generating a twinkling artifact signature. Doppler ultrasound data are obtained using the ultrasound system by operating the ultrasound system with the selected imaging parameters. The Doppler ultrasound data are obtained from a region-of-interest (“ROI”) containing a marker that when insonated with ultrasound generates a twinkling artifact signature. The marker is then localized in the ROI based on the twinkling artifact signature.

The foregoing and other aspects and advantages of the present disclosure will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of illustration a preferred embodiment. This embodiment does not necessarily represent the full scope of the invention, however, and reference is therefore made to the claims and herein for interpreting the scope of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 show an example of a non-metallic ultrasound-detectable marker according to some embodiments described in the present disclosure.

FIG. 2 is an example Doppler ultrasound image showing a twinkling signature generated by a marker constructed according to some embodiments described in the present disclosure.

FIG. 3 shows micro-CT images of an example marker composed of PMMA and cut to size using a laser cutting technique.

FIG. 4 shows scanning electron microscope images of the marker shown in FIG. 3.

FIG. 5 shows an example marker composed as a three-dimensional lattice of non-metallic material.

FIG. 6 shows examples of markers constructed to have wave-like protrusions.

FIG. 7 shows an example of a marker constructed using an additive manufacturing process, such as 3D printing, in which one or more voids (e.g., pores, apertures, hollow tubes) are formed as features within the body of the marker.

FIG. 8 is a Doppler ultrasound image of an example marker that is partially coated with PDMS, such that the PDMS coated part of the marker shows a “snowstorm” appearance and no twinkling, but the remainder of the marker maintains twinkling signature.

FIG. 9 is a flowchart setting forth the steps of an example method for locating or otherwise detecting non-metallic markers using ultrasound.

FIG. 10 is a block diagram of an example marker localization system.

FIG. 11 is a block diagram of example components that can implement the marker localization system of FIG. 10.

FIG. 12 is an example ultrasound system that can be used to detect the non-metallic markers described in the present disclosure.

DETAILED DESCRIPTION

Described here are markers (e.g., treatment site markers, biopsy site markers, fiducial markers, localizers) that are composed of a non-metallic material having a composition and/or other features or characteristics such that the markers will generate twinkling artifacts when imaged with ultrasound, in this way, the composition of the markers enables their detection and localization using ultrasound. The markers are generally composed of non-metallic materials whose physical and/or chemical properties enhance the twinkling artifact, thereby resulting in a twinkling “signature” that can be readily detected with ultrasound imaging. Advantageously, the markers are composed of a material that will produce consistent and obvious “pointers” in an ultrasound image using the twinkling artifact phenomenon. As such, these twinkling artifacts delineate the position of a marker placed within a region-of-interest, such as a lymph node or breast lesion, prior to and/or after treatment, such as neoadjuvant treatment.

In some implementations, the ultrasound system being used can be configured to provide haptic and/or audio feedback for the user during a procedure. For instance, the ultrasound system can be configured to detect the twinkling artifact from an implanted marker and in response generate a haptic response, an audio feedback signal, or both. Clinical procedural applications include but are not limited to surgery, radiation oncology, non-image guidance, needle-based or catheter-based interventions, and use in non-medical devices.

It is another aspect of the present disclosure to provide markers that can be constructed with features that can be tuned to a specific frequency so that ultrasound can insonate specifically at that frequency allowing for reliable detection.

Referring to FIG. 1, an example of a marker 10 that can be implemented in accordance with some embodiments of the present disclosure is illustrated. The marker 10 can have any suitable shape, including a generally cylindrical shape, a rectangular shape, a spherical shape, an ellipsoidal shape, a spiral shape, a coiled shape, a threaded shape, a helical shape, and so on. In other implementations, the marker 10 can be a clip or other instrument or device for implantation or insertion. For instance, the marker 10 can in some examples be a biopsy clip. In some implementations, the marker 10 can be sized to fit in standard needles for implantation, such as an 18-gauge needle. In other implementations, the marker 10 can be adhered, affixed, or otherwise coupled to a medical instrument or device to facilitate localization, guidance, and/or tracking of that medical instrument or device using ultrasound. In still other implementations, described in more detail below, the marker 10 can be a coating that is applied to another object, which may include a metallic marker.

As a non-limiting example, the medical instrument can be any suitable instrument or other medical devices used in a medical procedure or medical practice. As a non-limiting example, the medical instrument and/or device can include any metallic or non-metallic implantable or insertable instrument or device, such as markers; clips, including biopsy clips; wires, needles, including biopsy needles and brachytherapy needles; tubing; drains; tubes; catheters; endoscopic capsules; cardiac pacer leads; implants; sutures; prosthetic valves; and combinations thereof.

In general, the marker 10 is composed of a suitable non-metallic material that will cause the marker 10 to generate a twinkling artifact when imaged using ultrasound, such as Doppler ultrasound, as shown in FIG. 2. For instance, the marker 10 can be composed of a non-metallic material having formed therein features 12 that are constructed to generate twinkling artifacts. As one example, the features can be air bubbles, or other gas-filled or fluid-filled bubbles. In general, the features 12 can be inherent physical and/or chemical characteristics of the material from which the marker 10 is composed. Additionally or alternatively, the features 12 can include fractures, cracks, pockets, pores, or other deformations, which may be filled with air or other gases or fluids. The features 12 can be formed entirely internal to the body 14 of the marker 10, or can be formed such that they extend to and at least partially break the outer surface 16 of the marker 10.

in some implementations, the features 12 are filled with a gas that is selected to be slowly diffusing from the marker 10 into the tissue. The gas can be trapped in the body 14 of the marker 10 using chemical engineering techniques, mechanical techniques, or the like. For instance, the features 12 can be mechanically formed in the body 14 of the marker 10, such as by applying a suitable stress, strain, pressure, or other mechanical force to the body 14 of the marker.

As described above, the marker 10 is composed of a non-metallic material into which features 12 such as bubbles, fractures, cracks, pockets, pores, or other deformations are formed. In general, non-metallic materials exclude those materials that are entirely or substantially composed of elemental metals or metal alloys. As described below, however, non-metallic materials can include trace or other small amounts of metal, such as when doping the non-metallic material with metal-based contrast agents (e.g., contrast agents containing metal salts, metal chelates, and the like). The material can be any suitable non-metallic and biocompatible material. Advantageously, the features 12 are physical and/or chemical characteristics of the body 14 itself (i.e., of the materials of which the body 14 is composed). In some implementations, the marker 10 can be composed of biodegradable materials, such that the marker 10 will naturally breakdown when inserted into a subject's tissue.

As one example, the material can be a porous polymer, such as bone cement, or polymethyl methacrylate (“PMMA”). The PMMA may in some instances be etched (e.g., H₂SO₄ etched PMMA) and/or effervescent PMMA. Advantageously, the pores in such a porous polymer can act as the features 12 that are constructed to generate twinkling artifacts. Markers 10 composed of PMMA or other porous polymers can be manufactured using laser cutting or other fabrication techniques (e.g. including extrusion as an example, such as extruding a marker from a syringe or other suitable vessel or former) to form the markers 10 from a substrate of porous polymer. An example of a marker 10 composed of a porous polymer is shown in FIG. 3. This marker 10 was made from a thin wafer of PMMA and cut to size using laser technology. The surface roughness and the internal pores can be seen on this micro-CT image performed at 5 micrometer resolution. FIG. 4 shows scanning electron microscope images of the marker shown in FIG. 3. The SEM images shows the presence of pores, fractures, and surface roughness in the marker. In some implementations, images of a porous polymer marker can be used to generate 3D printing instructions; that is, the images can be used as source data for a 3D printed marker.

As another example, the material can be artificial uric acid. As one non-limiting example, the marker 10 can be composed of artificial uric acid that has been prepared by compressing the artificial uric acid under pressure, such as a pressure between 150-450 MPa. As still another example, the marker 10 can be composed of a resin, such as a dental composite resin or other synthetic resin.

In some instances, the marker 10 can be manufactured using an additive manufacturing process, such as 3D printing, stereolithography (SLA), or the like. As one non-limiting example, the marker 10 can be manufactured using SLA or other 3D printing techniques in order to form the body 14 of the marker 10 as having a plurality of pores as the features 12 that are constructed to generate twinkling artifacts. The pores may be micrometer sized pores, millimeter sized pores, or combinations thereof. As one non-limiting example, the pores can be sized to have diameters between 0.5 mm and 1 mm, such as 0.5 mm, 0.6 mm, or 1 mm. In another non-limiting example, the pores can have diameters in the range of 1 μm to 500 μm, which in some instances may be in the range of 1 μm to 80 μm. The pores may be uniform in size, or may have different sizes throughout the body 14 of the marker 10.

As another non-limiting example, the marker 10 can be manufactured using SLA or other 3D printing techniques in order to form the body 14 of the marker 10 as having a plurality of extruded and/or protruded surface features as the features 12 that are constructed to generate twinkling artifacts. For example, the body 14 can be constructed to have protrusions on the outer surface 16 of the body 14, such as wave-like protrusion; straight-line extrusions, which may form a grid or otherwise intersect with each other; or the like. In the example shown in FIG. 5, the marker 10 is constructed as a three-dimensional gridded structure, such as a grid lattice structure. In the examples shown in FIG. 6, the markers 10 are constructed to have wave-like protrusions on the outer surface. As shown, the markers 10 may also include apertures or other openings in the body 14.

As still another non-limiting example, the marker 10 can be manufactured using SLA or other 3D printing or additive manufacturing techniques in order to form the body 14 of the marker 10 as shown FIG. 7. In this example, the features 12 that are constructed to generate twinkling artifacts can include pores 70 or other apertures formed in the outer surface 16 of the body 14 and/or contained within the inner volume of the body 14. The features 12 can also include one or more hollow tubes 72 that are formed within the body 14. The hollow tube(s) 72 may be formed. to be contained completely within the inner volume of the body 14, or may extend to the outer surface 16 of the body 14, such that the hollow tube(s) 72 form an opening (e.g., an aperture) at the outer surface 16 of the body 14. The hollow tube(s) 72 may have a regular and/or uniform shape, or may have an arbitrary shape, such as shown in the example of FIG. 7. More generally, other forms of voids in the fill material used in the additive manufacturing process may also be used. The body 14 may also be constructed to have a rough texture on the outer surface 16, such as ridges 74, bumps, or other surface features. In the example shown in FIG. 7, the outer surface 16 has a coiled appearance formed by a series of regular ridges 74.

In some other instances, one or more features 12 may be formed in the body 14 of the marker 10. As one example, one or more features 12 may be formed in the body 14 by microetching or other such fabrication techniques. As another example, one or more features 12 may be formed in the body 14 by adding micro air bubbles (or other gas-filled bubbles) into a substrate that forms the body 14. As still another example, one or more features 12 may be formed in the body 14 by leaching pores into the body 14 of the marker. For instance, features 12 may be formed by leaching (e.g., salt leaching) on cross-linked polydimethylsiloxane (“PDMS”), PMMA, or another suitable substrate.

The outer surface 16 of the marker 10 can be smooth, or in some other implementations can be textured. In some implementations, the outer surface 16 of the marker 10 can be coated with one or more coatings.

Thus, as described, in some embodiments the marker 10 cart include a textured surface or internal features that are designed to augment the twinkling signature. The texture (e g., surface roughness features) can be created mechanically through coating, etching (e.g., H₂SO₄ etching), additive manufacturing (e.g., 3D printing), photolithography, or using a laser. Surface roughness features can be measured by 3D coherence scanning, confocal laser microscopy, interferometer optical profiler, holographic microscopy, micro-CT, or scanning electron microscopy (“SEM”).

To facilitate imaging of the marker 10 with imaging modalities other than ultrasound (e.g., x-ray, CT, MRI) as may be done in the routine treatment process, the marker 10 can be doped with a suitable contrast agent. As one example, the marker 10 can be composed of a non-metallic material that is doped with an x-ray contrast agent, such as barium sulfate or another radiopaque contrast agent. As another example, the marker 10 can be composed of a non-metallic material that is doped with gadolinium, iron oxide, or another paramagnetic contrast agent used in magnetic resonance imaging. As still another example, the marker 10 can be doped with a dye, such as a visible dye to color the marker or a fluorescent dye or quantum dots that can be imaged. As still another example, the outer surface 16 of the marker 10 can be coated, partially or completely, with one or more coatings that will enhance the appearance of the marker 10 in another imaging modality, such as x-ray, CT, or MRI. For instance, the marker 10 can be at least partially coated with a coating that will enhance the MRI signal of the marker 10. As non-limiting examples, the coating could include silicone-based signaling compounds, saline, vitamin E, and iron-based compounds, such as Feraheme and/or ferumoxytol, which demonstrates T₁ relaxation and can be used in varying doses as contrast for mapping of superficial lymphatic vessels in patients with extremity lymphedema.

Additionally or alternatively, the marker 10 can be constructed to serve as the foundation for additional signaling or as a source of therapeutic agents.

In some implementations, the marker 10 can be constructed such that it can be anchored within a tissue. In this way, the marker 10 can be made to remain adjacent a marked lesion even when that lesion shrinks over time as a result of treatment delivered to the lesion region. That is, the marker 10 can be anchored to a tissue so as to prevent or otherwise minimize migration of the marker 10.

As one non-limiting example, a material that causes a local inflammatory reaction can be coupled to the marker 10 such that when the marker 10 is implanted it will be anchored in position via mild soft-tissue matting. For instance, a polypropylene mesh material, such as PROLENE® (Johnson & Johnson Corporation; New Brunswick, N.J., United States) can be coupled to the marker 10 to achieve this effect. Only a small amount of mesh material can be used to induce such a reaction. The mesh material can be coupled to a single side (or surface) of the marker 10, or more than one side (or surface) of the marker 10.

As another non-limiting example, the marker 10 can be composed of and/or coated in, whether partially or fully, a material that reduces migration of the marker. In an example implementation, polydimethylsiloxane (“PDMS”) can be used to reduce migration of the marker 10 when implanted. Alternatively, other materials can be used, including ethanol. PDMS has a low chemical activity and is biologically inert, which is useful when it is used in implant devices. PDMS is made from a 3-component system involving a base, a curing agent, and a catalyst. The base is predominantly dimethylvinyl-terminated dimethylsiloxane. The curing agent is mostly composed of dimethylhydrogen siloxane. Both of these can be mixed with additives depending on the desired mechanical properties of the cured polymer. The third component is generally a metal-centered catalyst to promote crosslinking. For example, the metal-centered catalyst may be a platinum complex that promotes a hydrosilylation reaction between the methyl hydrogen siloxane units in the curing agent and the terminal vinyl groups in the base siloxane.

An interesting property of cured PDMS is its ability of adhesion, hydrophobic properties, and low density compared to water and saline. In a semiaqueous environment (e.g., similar to human soft tissues), PDMS can make physical connections with solid surfaces. Based on these properties, the markers 10 can be coated on one or more surface with PDMS in order to achieve anchoring properties. In addition, PDMS exhibits ultrasound signaling features that are similar to free silicone; namely, a “snowstorm” appearance, which can be readily recognized during diagnostic ultrasound imaging. Based on this property; partially coating a marker 10 with PDMS can provide additional imaging characteristics.

One example marker 10 was constructed as follows. The marker 10 was laser cut from a PMMA wafer and then partially coated with PDMS mixture and cured for 4 hours at 65 degrees Celsius. The sonographic appearance of this marker 10 demonstrated the classic “snowstorm appearance” of silicone as well as the twinkling signature described in the present disclosure, as shown in FIG. 8. It is contemplated that such a dual signaling (silicone and twinkling) marker 10 will not only afford greater sonographic detectability, but will also create a means by which migration of the marker will be minimized. In some configurations, a small amount of PDMS can be added as a concentric ring around the marker 10, such that a different number of PDMS rings could be used as a way to distinguish two markers 10 in relative close proximity to each other.

Further, in some implementations a plurality of markers 10 can be agglomerated, connected by filaments, or otherwise coupled together.

In some constructions, the marker 10 can be constructed to have one or more portions that can be turned to a certain frequency, such that when insonated by an ultrasound probe at that frequency those portions of the marker 10 can be reliably detected.

The examples described above include markers that are composed of non-metallic materials that are specifically composed to generate twinkling artifacts. In other examples, standard or otherwise existing markers, implants, medical instruments, or devices can be coated in a similar non-metallic material that is composed to generate twinkling artifacts. Examples of medical devices and/or instruments that can be coated or otherwise textured to generate a twinkling artifact include biopsy markers, biopsy clips (including Q clips (Tumark® Q, SOMATEX Medical Technologies, Berlin, Germany) and cork clips (TriMark® Cork, Hologic, Marlborough, Mass., USA)), fiducials, localizers, needles (including brachytherapy needles, scribed needles), guidewires, screws, files, and surgical rasps. Thus, as a non-limiting example, the marker 10 can include a marker coupled to a medical instrument or device, and/or a portion of a medical instrument or device that has been textured and/or coated to generate a twinkling artifact.

In other examples, radioactive seeds, such as those used for brachytherapy treatments, can be coated with a similar non-metallic material that is composed to generate twinkling artifacts, which can facilitate the localization and accurate placement of these radioactive seeds. In addition to providing brachytherapy treatment, radiation seeds (e.g., I-125 seeds) can be used in preoperative localization to help guide a surgeon in the operating room. Currently, radioactive I-125 seed placements are capped (e.g., at 2 or 3) because surgeons are unable to precisely resolve the positions of radioactive seeds in the operating room when there are too many radioactive seeds in close proximity to each other. Using radioactive seeds coated with the materials described in the present disclosure can overcome this problem by enabling better localization of individual seed placement, even when more than 2 or 3 seeds are used. Moreover, the materials described in the present disclosure can serve as the localizers themselves, thereby obviating the need for preoperative radioactive seed localization.

In some implementations, in addition to forming features 12 in the body 14 of the marker 10, microspheres may be embedded in the body 14 to further enhance the twinkling signature generated by the marker 10. As one example, the microspheres could be titanium microspheres or other metallic microspheres. As another example, the microspheres could be polylactic-co-glycolic acid) (“PLGA”) or other polymer or copolymer microspheres. In some embodiments, the marker 10 could be composed starting with such microspheres and forming the non-metallic substrate as a binder material.

Having described example markers, a method for using such markers is now described. Referring to FIG. 9, a flowchart is illustrated as setting forth the steps of an example method for detecting a non-metallic marker using ultrasound. The method includes inserting one or more markers into a tissue region within a subject, as indicated at step 902. The markers may be inserted via injection using a needle or via deployment using a coaxial needle and inner stylet. As noted above, the needle may be an 18-gauge needle in some implementations.

When the one or more markers are in place, ultrasound data are acquired from a region-of-interest containing the markers, as indicated at step 904. In general, the ultrasound data are Doppler ultrasound data, such as color Doppler, power Doppler, or spectral Doppler ultrasound data. The ultrasound data may include, for instance, images that depict the region-of-interest. Because of the material composition of the markers, twinkling artifacts will be present in these images. The location of the one or more markers can then be detected by analyzing the images in the ultrasound data, as indicated at step 906. For instance, the twinkling artifacts can point to the location of the marker that is generating the twinkling artifact, thereby enabling localization of the marker.

in some non-limiting examples, the locations of the one or more markers can be detected by inputting the ultrasound data to a suitably trained machine learning algorithm, generating output as feature data or a feature map indicating the location of the one or more markers. In these instances, the machine learning algorithm can be trained to detect the twinkling artifacts. For instance, the machine learning algorithm could be trained on training data that includes labeled ultrasound images that indicate the presence and location of twinkling artifacts. The machine learning algorithm may be an artificial neural network, such as a convolution neural network. In some implementations, the machine learning algorithm may implement deep learning. Using this suitably trained machine learning algorithm can enable automatic, real-time detection and localization of multiple different markers.

The locations of the markers can be recorded and stored for later use, as indicated at step 908. In some implementations, the locations of the markers can be stored and used to generate a display element that indicates the location or otherwise depicts of each marker. These display elements can then be generated on a display for a user to visualize the location of the markers within the imaged region-of-interest. In some other implementations, the locations of the markers can be stored and coregistered with other medical images (e.g., x-ray images, CT images, magnetic resonance images) in order to visualize the markers on those other medical images.

In still other implementations, the locations of the markers can be stored and converted into coordinate data for use with a surgical navigation system or a guided radiation therapy system. In this way, the coordinate data associated with the locations of the markers as determined from the ultrasound images of those markers can be used to guide accurate delivery of treatment to the subject.

The readily identifiable twinkling signature on color flow imaging associated with the markers described in the present disclosure can be translated into an apparent acoustic signature. For instance, the twinkling signature can be translated into an acoustic signature by using a pulsed Doppler gate, or by using other suitable image processing techniques to detect twinkling present in the color flow imaging region-of-interest (“ROI”). As described below, using ultrasound imaging parameters that are optimized to generate a twinkling artifact signature, twinkling artifacts can be identified. and analyzed without the use of an acoustic gate.

Advantageously, using this technique the twinkling signature's variability in time and space can be used to sensitively and specifically identify the marker and avoid false positive signals. In some implementations, the acoustic gate can also be modulated to explore various depths and detect the twinkling sound. Digital signal processing algorithms and techniques can also be implemented to reflect a continuous readout to the user of the distance from the probe to the twinkling source. This can enable the user to accurately locate the marker in real-time based on the acoustic feedback provided by the twinkling signature. In a similar fashion, haptic feedback can be generated and provided to the user to help indicate the location of the marker 10. The acoustic signature can be used as a broadband sound from the ultrasound machine or a tone could be used and the tone could be modulated in amplitude or repetition to indicate proximity of the ultrasound transducer to the marker.

Color flow imaging (CFI) or power Doppler (PD) both use pulsed Doppler techniques to measure blood flow velocity. The twinkling signatures described in the present disclosure have high spatial and temporal variability of the velocity map produced by the CFI or PD modes. This spatiotemporal variation can be utilized to identify regions in an image exhibiting such twinkling signatures, which can be used for localization, for generating acoustic feedback, and/or for generating haptic feedback related to a localized marker.

On a pixel-by-pixel basis, a window of N_(t) frames can be isolated and the variance, V_(t), can be calculated using the equations below.

$\begin{matrix} {{{V_{t}\left( {x,y,n} \right)} = {\frac{2}{N_{t} - 1}{\sum\limits_{i = {n - {{({N_{t} - 1})}/2}}}^{n + {{({N_{t} - 1})}/2}}\;{{{I\left( {x,y,i} \right)} - \mu}}^{2}}}};} & (1) \\ {\mu = {\frac{1}{N}{\sum\limits_{i = {n - {{({N_{t} - 1})}/2}}}^{n + {{({N_{t} - 1})}/2}}{{I\left( {x,y,i} \right)}.}}}} & (2) \end{matrix}$

In this formulation the value of N_(t) is odd. When N_(t) is even, the expressions in Eqns. (1) and (2) can be adjusted so that the limits may be N_(t)/2 and n+N_(t)/2. The variance value for the N_(t) frames will replace the pixel value for the middle of the window.

On a frame-by-frame basis, a moving two-dimensional (2D) window of N_(s)×N_(s) pixels can be isolated and a variance, V_(s), can be calculated. In the formulation below, N_(s) is odd.

$\begin{matrix} {{{V_{s}\left( {x,y,n} \right)} = {\frac{2}{N_{s}^{2} - 1}{\sum\limits_{i = {x - {{({N_{s} - 1})}/2}}}^{x + {{({N_{s} - 1})}/2}}{\sum\limits_{j = {y - {{({N_{s} - 1})}/2}}}^{y + {{({N_{s} - 1})}/2}}\;{{{I\left( {i,j,n} \right)} - \mu}}^{2}}}}};} & (3) \\ {\mu = {\frac{1}{N_{s}^{2}}{\sum\limits_{i = {x - {{({N_{s} - 1})}/2}}}^{x + {{({N_{s} - 1})}/2}}{\sum\limits_{j = {y - {{({N_{s} - 1})}/2}}}^{y + {{({N_{s} - 1})}/2}}{{I\left( {i,j,n} \right)}.}}}}} & (4) \end{matrix}$

As above, when N_(s) is even, the expressions in Eqns. (3) and (4) can be adjusted such that the limits are x−N_(s)/2 to x+N_(s)/2 and y−N_(s)/2 to y+N_(s)/2. The variance value for the 2D window will replace the value for the middle pixel of the window at (x, y).

On a pixel-by-pixel and frame-by-frame basis the temporal and spatial variance, V_(ts), can be combined in some way either by sum or product. An example combined metric can be provided by:

V _(ts)(x, y, n)=V _(t)(x, y, n)V _(s)(x, y, n)   (5).

After the different metrics are evaluated, a threshold can be determined for masking pixels in an ultrasound cine clip to show where the metric has determined the presence of twinkling.

It is contemplated that the temporal variance is the most sensitive; however, the combination of spatial and temporal variance can improve specificity of the metric to eliminate noise and/or false positives.

Medical devices are often not well seen by standard routine B-mode ultrasound imaging. The systems and methods described in the present disclosure overcome this limitation by providing ultrasound visible markers. Additionally, technical ultrasound specifications that are optimized to elicit and consistently reproduce twinkling artifacts of such markers in different media are provided. These technical ultrasound specifications can include one or more imaging parameter settings (e.g., choice and combination of imaging parameters to set, values for particular imaging parameters), the particular type or design of ultrasound transducer to use for imaging, and/or the type of ultrasound technique to implement.

The systems and methods described in the present disclosure can implement any number of suitable ultrasound transducer types, including broad-spectrum linear transducers, broad-spectrum linear matrix-array transducers, curvilinear array transducers, endocavity transducers endocavity biplane transducers), and so on.

Advantageously, curvilinear array transducers may be particularly useful for generating a twinkling artifact signature as compared to linear arrays. As such, these transducers may be particularly useful for rapid detection of twinkling.

A broad-spectrum linear transducer may allow for reasonable assessment for twinkling with better resolution. As such, these transducers may be particularly useful for those applications where a higher degree of spatial accuracy is desirable.

Although curvilinear transducer arrays have found use in a range of clinical applications, they are not routinely used in breast radiology applications. It is a discovery that the systems and methods described in the present disclosure provide unique advantages for breast radiology applications, such as localizing and/or tracking biopsy clips, biopsy needles, brachytherapy needles, or other medical instruments that may be used in breast radiology applications. As a non-limiting example, a curvilinear transducer array, which may not be traditionally used for breast radiology applications, may be the optimal transducer for generating a twinkling artifact in breast. radiology applications. Thus, in some instances, it is an advantage of the systems and methods described in the present disclosure to use a curvilinear transducer array in breast radiology applications where such transducer arrays would otherwise not have traditional clinical utility. Furthermore, the systems and methods described in the present disclosure provide other advantages over convention breast radiology applications, which traditionally do not implement Doppler ultrasound (e.g., pulse-wave Doppler ultrasound) except for vascular assessment.

The twinkling signature described in the present disclosure allows for consistent detection of markers, or medical devices having markers coupled thereto, with ultrasound. The technical ultrasound specifications are designed to be optimizable particularly for generating a detectable twinkling artifact signature over a range of imaging parameters (e.g., color ultrasound transmit frequency, color gain, color scale, wall filter, threshold, color-write priority, Power Doppler, pulse repetition frequency, focal zone, field-of-view, color flow region-of-interest), or related to underlying ultrasound techniques (e.g., high-frequency).

In general, the technical ultrasound specifications are designed or otherwise selected to prioritize imaging parameters that optimize the generation of a twinkling artifact signature. That is, in some implementations the technical ultrasound. specifications are optimized to purposefully generate a twinkling artifact that for traditional imaging applications would be viewed as an undesired result. However, the systems and methods disclosed in the present disclosure intentionally seek to generate a maximal twinkling artifact signature.

Setting the ultrasound technical specifications can include designing or otherwise selecting one or more imaging parameters that are preferentially sensitive to increasing a twinkling artifact signature. As a non-limiting example, these imaging parameters can include color ultrasound transmit frequency, color gain, and color scale. Additionally or alternatively, the values for other imaging parameters can also be selected. to affect the generation of a twinkling artifact signature, including threshold, wall filter, pulse repetition frequency, focal zone, field-of-view, and the color flow region-of-interest, as mentioned above.

In some implementations, the technical ultrasound specifications and/or optimized imaging parameters can be assessed by a discretized score that takes into account the degree of twinkling artifact generated (e.g., none, likely none, mild, moderate, exuberant) and the diagnostic confidence of twinkling artifact generation. For example, a scoring scale can range from 0 to 4 can be used, with: 0 (confident no twinkling); 1 (not confident, likely no twinkling); 2 (confident mild twinkling); 3 (confident moderate twinkling with some cornet tail and nearly overlying the entire B-mode target); and, 4 (confident exuberant twinkling with comet tail and completely overlying the B-mode target). The disclosed ultrasound technical specifications produce a twinkling signature that allows for non-gated acoustic signal and haptic feedback with a single button operation.

As one example, the ultrasound transducer can be a broad-spectrum linear (2 MHz-8 MHz) transducer. As another example, the ultrasound transducer can be a broad-spectrum linear matrix-array (4 MHz-15 MHz) transducer. As yet another example, the ultrasound transducer can be a curvilinear array (1 MHz-6 MHz) transducer.

A single focal zone can be used. In an example configuration, the focus can be placed within a centimeter posterior to the marker. The field-of-view can be set to cover the desired region-of-interest. As a non-limiting example, the field-of-view can be set to about 4 cm deep for applications such as axillary lymph node imaging. For color flow imaging, the width of the region-of-interest can be set to approximately half of the width of the image, and the height of the color region-of-interest can be set to allow for a reasonable refresh rate. As a non-limiting example, the height of the region-of-interest can be approximately 2 cm.

For each marker, the threshold (also called color-write priority), wall filter, color scale, ultrasound transmit frequency, and gain can be varied to optimize twinkling. As a non-limiting example, when using a broad-spectrum linear transducer (e.g., 2-8 MHz), the following default settings can be used:

Optimized Default Settings for Broad-Spectrum Linear Transducer

Parameter Default Setting Threshold 90% Wall Filter 52 Hz Color Scale ±6 cm/s Color Ultrasound Transmit Frequency 4.2 MHz Color Gain 16 dB

The ranges of setting options available when using a broad-spectrum linear transducer (e.g., 2-8 MHz) can include the following:

Parameter Setting Ranges for Broad-Spectrum Linear Transducer

Parameter Setting Range Threshold [0, 10, 20, . . . , 90, 100]% Wall Filter [35, 52, 69, 87, 96] Hz Color Scale [±1, ±2, ±3, ±4, ±5, ±6, ±8, ±9, ±12, ±15, ±20, ±30, ±40, ±50, ±75, ±100] cm/s Color Ultrasound [3.1, 3.6, 4.2, 5.0, 63] MHz Transmit Frequency Color Gain [−20.0, −19.5, −19.0, . . . , 29.0, 29.5, 30.0] dB [0, 5, 10, 15, 20, 25, . . . , 85, 90, 95, 100]%

As a non-limiting example, when using a broad-spectrum linear matrix-array transducer (4-15 MHz), the following default settings can be used:

Optimized Default Settings for Broad-Spectrum Linear Matrix-Array Transducer

Parameter Default Setting Threshold 90% Wall Filter 59 Hz Color Scale ±5 cm/s Color Ultrasound Transmit Frequency 6.3 MHz Color Gain 21 dB

The ranges of setting options available when using a broad-spectrum linear matrix-array transducer (4-15 MHz) can include the following:

Parameter Setting Ranges for Broad-Spectrum Linear Matrix-Array Transducer

Parameter Setting Range Threshold [0, 10, 20, . . . , 90, 100]% Wall Filter [51, 59, 89, 118, 148] Hz Color Scale [±1, ±2, ±3, ±4, ±5, ±6, ±8, ±9, ±12, ±15, ±20, ±30, ±40, ±50, ±75, ±77] cm/s Color Ultrasound [5.0, 6.3, 6.5, 7.5, 8.3, 10.0, 12.5] MHz Transmit Frequency Color Gain [−20.0, −19,5, −19.0, . . . . , 29.0, 29.5, 30.0] dB [0, 5, 10, 15, 20, 25, . . . , 85, 90, 95, 100]%

As a non-limiting example, when using a curvilinear array transducer (1 MHz-6 MHz), the following default settings can be used:

Optimized Default Settings for Curvilinear Array Transducer

Parameter Default Setting Threshold 90% Wall Filter 209 Hz Color Scale ±18 cm/s Color Ultrasound Transmit Frequency 3.1 MHz Color Gain 21.0 dB

The ranges of setting options available when using a curvilinear array transducer (1 MHz-6 MHz) can include the following:

Parameter Setting Ranges for Curvilinear Array Transducer

Parameter Setting Range Threshold [0, 10, 20, . . . , 90, 100]% Wall Filter [208, 209, 211, 262] Hz Color Scale [±1, ±2, ±3, ±4, ±5, ±6, ±7, ±9, ±12, ±15, ±20, Color Ultrasound ±30, ±40, ±50, ±75, ±100] cm/s Transmit Frequency [1.7, 1.9, 2.1, 2.5, 3.1, 3.6] MHz Color Gain [−20.0, −19,5, −19.0, . . . . , 29.0, 29.5, 30.0] dB [0, 5, 10, 15, 20, 25, . . . , 85, 90, 95, 100]%

For example, color ultrasound transmit frequency settings may be selected from a range of about 2 MHz to about 13 MHz or ranges therebetween, such as 2 MHz to 4 MHz, 4 MHz to 6 MHz, 6 MHz to 8 MHz, and so on. In some embodiments, the color ultrasound transmit frequency can be selected as 3.1 MHz, 3.6 MHz, 4.2 MHz, 6 MHz, or 6.3 MHz. For instance, for a curvilinear array transducer the color ultrasound transmit frequency may be selected from a range of 2 MHz to 4 MHz, such as 2.1 MHz, 3.1 MHz, or 3.6 MHz; for a broad-spectrum linear transducer, the color ultrasound transmit frequency may be selected from a range of 3 MHz to 6 MHz, such as 3.1 MHz, 3.6 MHz, 4.2 MHz, or 5 MHz; and for a broad-spectrum linear matrix-array transducer, the color ultrasound transmit frequency may be selected from a range of 5 MHz to 12 MHz, such as 6.3 MHz. The color ultrasound transmit frequency setting can be selected from these ranges in increments of 1 MHz, 0.1 MHz, and so on. As an example, the color ultrasound transmit frequency can be selected as 6 MHz. This latter example may be advantageous for an endocavity ultrasound transducer, such as an endocavity biplane transducer.

For example, color gain settings may be selected from a range of about 12 dB to about 30 dB, or ranges therebetween, such as 12 dB to 18 dB, 18 dB to 22 dB, 22 dB to 25 dB, 25 dB to 30 dB, and so on. As another example, the color gain settings may be selected from a range of about 20 dB to about 30 dB. In some embodiments, the color gain can be selected as 19.5 dB, 20.5 dB, 21 dB, 21.5 dB, or 23 dB. For instance, for a curvilinear array transducer the color gain may be selected from a range of 12 dB to 24 dB, such as 14 dB, 19.5 dB, 20 dB, 21 dB, or 23 dB; for a broad-spectrum linear transducer, the color gain may be selected from a range of 18 dB to 25 dB, such as 19.5 dB, 20 dB, 21 dB, 21.5 dB, 22.5 dB, 23 dB, or 23.5 dB; and for a broad-spectrum linear matrix-array transducer, the color gain may be selected from a range of 18 dB to 25 dB, such as 20.5 dB, 21.5 dB, 23 dB, or 23.5 dB. The color gain setting can be selected from these ranges in increments of 1 dB, 0.5 dB, 0.1 dB, and so on. As an example, the color gain can be selected as 14 dB. This latter example may be advantageous for an endocavity ultrasound transducer, such as an endocavity biplane transducer.

Alternatively, color gain settings may be selectable as a percentage value rather than dB units. In these instances, the color gain settings may be selected from a range of 0% to 100%, or ranges therebetween, such as 20% to 40%, 40% to 60%, 60% to 80%, and so on. For example, color gain could be selected as 48%, 50%, 52%, or 60%. The color gain setting can be selected from these ranges in increments of 5%, 1%, 0.5%, 0.1%, and so on.

For example, color scale settings may be selected from a range of about ±1 cm/s to about ±100 cm/s, a range of about ±2 cm/s to about ±20 cm/s, or ranges therebetween, such as ±1 cm/s to ±6 cm/s, ±6 cm/s to ±20 cm/s, and so on. Alternatively, the color scale settings may be selected from a low, medium, or high range of values. In some embodiments, the color scale setting can be selected at ±3 cm/s, ±5 cm/s, ±6 cm/s, or ±18 cm/s. For instance, for a curvilinear array transducer the color scale may be selected from a range of ±4 cm/s to ±20 cm/s, such as ±6 cm/s, ±9 cm/s, or ±18 cm/s; for a broad-spectrum linear transducer, the color scale may be selected from a range of ±1 cm/s to ±8 cm/s, such as ±3 cm/s or ±6 cm/s; and for a broad-spectrum linear matrix-array transducer, the color scale may be selected from a range of ±3 cm/s to ±7 cm/s, such as ±5 cm/s. The color scale setting can be selected from these ranges in increments of ±1 cm/s, ±0.1 cm/s, and so on. As an example, the color scale setting can be selected as ±4.9 cm/s. This latter example may be advantageous for an endocavity ultrasound transducer, such as an endocavity biplane transducer.

Using a curvilinear array transducer, the following example configurations of these parameter settings may be used, in addition to other combinations of settings from the described ranges. It will be appreciated that an optimized combination of settings can be determined for a given transducer and a given imaging application (e.g., using different markers may result in different optimal parameter settings):

TABLE 1 Example Curvilinear Array Transducer Setting Configurations Color Transmit Color Gain Color Scale Frequency (MHz) (dB) (cm/s) 2.1 19.5 ±18 3.1 23 ±6 3.1 22 ±18 3.1 23 ±6 3.1 21 ±18 3.6 19.5 ±6 3.1 20 ±9 3.1 14 ±18

As another example, a curvilinear array transducer could be used with values of 5.0 MHz for color transmit frequency, 52% for color gain, and ±18 cm/s for color scale.

Using a broad-spectrum linear transducer, the following example configurations of these parameter settings may be used, in addition to other combinations of settings from the described ranges. It will be appreciated that an optimized combination of settings can be determined for a given transducer and a given imaging application (e.g., using different markers may result in different optimal parameter settings):

TABLE 2 Example Broad-Spectrum Linear Transducer Setting Configurations Color Transmit Color Gain Color Scale Frequency (MHz) (dB) (cm/s) 4.2 20 ±6 5.0 23.5 ±3 5.0 20.5 ±6 5.0 23.5 ±3 4.2 21.5 ±6 4,2 23 ±3 3.6 19.5 ±6 3.6 21 ±6 3.1 21 ±6 3.6 22.5 ±6

As another example, a broad-spectrum linear transducer could be used with values of 4.3 MHz for color transmit frequency,48% for color gain, and ±10.8 cm/s for color scale.

Using a broad-spectrum linear matrix-array transducer, the following example configurations of these parameter settings may be used, in addition to other combinations of settings from the described ranges. It will be appreciated that an optimized combination of settings can be determined for a given transducer and a given imaging application (e.g., using different markers may result in different optimal parameter settings):

TABLE 3 Example Broad-Spectrum Linear Matrix-Array Transducer Setting Configurations Color Transmit Color Gain Color Scale Frequency (MHz) (dB) (cm/s) 6.3 21.5 ±7 6.3 23.5 ±5 6.3 22 ±5 6.3 22.5 ±5 6.3 20.5 ±5 6.3 23 ±5

As another example, a broad-spectrum linear matrix-array transducer could be used with values of 6.5 MHz for color transmit frequency, 63% for color gain, and ±4.4 cm/s for color scale.

In still other implementations, other ultrasound transducer types can be used. For each ultrasound transducer, a different set of parameter settings may result in optimal twinkling response. As another example, an endocavity ultrasound transducer may be used, such as an endocavity biplane transducer. As a non-limiting example, a color transmit frequency of 6 MHz, color gain of 14 dB, and color scale of ±4.9 cm/s may be used; however, it will be appreciated that other values may also be selected depending on the imaging application at hand and the particular marker being imaged.

When there is no discernible twinkling difference between the default and other settings, the default setting can be used. Otherwise, an updated setting can be selected from the optimized ranges for a particular parameter setting, and the updated setting can be compared against the other settings if desired.

In some configurations, rather than independently modulating the pulse repetition frequency setting, this setting can be modulated by color scale and/or color ultrasound transmit frequency selections.

Referring now to FIG. 10, an example of a system 1000 for detecting or otherwise locating a marker (e.g., a treatment site marker, a biopsy site marker) in accordance with some embodiments of the systems and methods described in the present disclosure is shown. As shown in FIG. 10, a computing device 1050 can receive one or more types of data (e.g., ultrasound data) from ultrasound image source 1002. In some embodiments, computing device 1050 can execute at least a portion of a marker localization system 1004 to locate one or more markers from data received from the ultrasound image source 1002.

Additionally or alternatively, in some embodiments, the computing device 1050 can communicate information about data received from the ultrasound image source 1002 to a server 1052 over a communication network 1054, which can execute at least a portion of the marker localization system 1004. In such embodiments, the server 1052 can return information to the computing device 1050 (and/or any other suitable computing device) indicative of an output of the marker localization system 1004.

In some embodiments, computing device 1050 and/or server 1052 can be any suitable computing device or combination of devices, such as a desktop computer, a laptop computer, a smartphone, a tablet computer, a wearable computer, a server computer, a virtual machine being executed by a physical computing device, and so on. The computing device 1050 and/or server 1052 can also reconstruct images from the data.

In some embodiments, ultrasound image source 1002 can be any suitable source of image data (e.g., measurement data, images reconstructed from measurement data), such as an ultrasound system, another computing device (e.g., a server storing image data), and so on. In some embodiments, ultrasound image source 1002 can be local to computing device 1050. For example, ultrasound image source 1002 can be incorporated with computing device 1050 (e.g., computing device 1050 can be configured as part of a device for capturing, scanning, and/or storing images). As another example, ultrasound image source 1002 can be connected to computing device 1050 by a cable, a direct wireless link, and so on. Additionally or alternatively, in some embodiments, ultrasound image source 1002 can be located locally and/or remotely from computing device 1050, and can communicate data to computing device 1050 (and/or server 1052) via a communication network (e.g., communication network 1054).

In some embodiments, communication network 1054 can be any suitable communication network or combination of communication networks. For example, communication network 1054 can include a Wi-Fi network (which can include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, etc., complying with any suitable standard, such as CDMA, GSM, LTE, LTE Advanced, WiMAX, etc.), a wired network, and so on. In some embodiments, communication network 108 can be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a corporate or university intranet), any other suitable type of network, or any suitable combination of networks. Communications links shown in FIG. 10 can each be any suitable communications link or combination of communications links, such as wired links, fiber optic links, Wi-Fi links, Bluetooth links, cellular links, and so on.

Referring now to FIG. 11, an example of hardware 1100 that can be used to implement ultrasound image source 1002, computing device 1050, and server 1052 in accordance with some embodiments of the systems and methods described in the present disclosure is shown. As shown in FIG. 11, in some embodiments, computing device 1050 can include a processor 1102, a display 1104, one or more inputs 1106, one or more communication systems 1108, and/or memory 1110. In some embodiments, processor 1102 can be any suitable hardware processor or combination of processors, such as a central processing unit (“CPU”), a graphics processing unit (“GPU”), and so on. In some embodiments, display 1104 can include any suitable display devices, such as a computer monitor, a touchscreen, a television, and so on. In some embodiments, inputs 1106 can include any suitable input devices and/or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, and so on.

In some embodiments, communications systems 1108 can include any suitable hardware, firmware, and/or software for communicating information over communication network 1054 and/or any other suitable communication networks. For example, communications systems 1108 can include one or more transceivers, one or more communication chips and/or chip sets, and so on. In a more particular example, communications systems 1108 can include hardware, firmware and/or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

In some embodiments, memory 1110 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 1102 to present content using display 1104, to communicate with server 1052 via communications system(s) 1108, and so on. Memory 1110 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 1110 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some embodiments, memory 1110 can have encoded thereon, or otherwise stored therein, a computer program for controlling operation of computing device 1050. In such embodiments, processor 1102 can execute at least a portion of the computer program to present content (e.g., images, user interfaces, graphics, tables), receive content from server 1052, transmit information to server 1052, and so on.

In some embodiments, server 1052 can include a processor 1112, a display 1114, one or more inputs 1116, one or more communications systems 1118, and/or memory 1120. In some embodiments, processor 1112 can be any suitable hardware processor or combination of processors, such as a CPU, a GPU, and so on. In some embodiments, display 1114 can include any suitable display devices, such as a computer monitor, a touchscreen, a television, and so on. In some embodiments, inputs 1116 can include any suitable input devices and/or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, and so on.

In some embodiments, communications systems 1118 can include any suitable hardware, firmware, and/or software for communicating information over communication network 1054 and/or any other suitable communication networks. For example, communications systems 1118 can include one or more transceivers, one or more communication chips and/or chip sets, and so on. In a more particular example, communications systems 1118 can include hardware, firmware and/or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

In some embodiments, memory 1120 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 1112 to present content using display 1114, to communicate with one or more computing devices 1050, and so on. Memory 1120 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 1120 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some embodiments, memory 1120 can have encoded thereon a server program for controlling operation of server 1052. In such embodiments, processor 1112 can execute at least a portion of the server program to transmit information and/or content (e.g., data, images, a user interface) to one or more computing devices 1050, receive information and/or content from one or more computing devices 1050, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone), and so on.

In some embodiments, ultrasound image source 1002 can include a processor 1122, one or more ultrasound transducers 1124, one of more communications systems 1126, and/or memory 1128. In some embodiments, processor 1122 can be any suitable hardware processor or combination of processors, such as a CPU, a GPU, and so on. In some embodiments, the one or more ultrasound transducers 1124 are generally configured to acquire data, images, or both. Additionally or alternatively; in some embodiments, one or more ultrasound transducers 1124 can include any suitable hardware, firmware, and/or software for coupling to and/or controlling operations of an ultrasound transducer. In some embodiments, one or more portions of the one or more ultrasound transducers 1124 can be removable and/or replaceable.

Note that, although not shown, ultrasound image source 1002 can include any suitable inputs and/or outputs. For example, ultrasound image source 1002 can include input devices and/or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, a trackpad, a trackball, and so on. As another example, ultrasound image source 1002 can include any suitable display devices, such as a computer monitor, a touchscreen, a television, etc., one or more speakers, and so on. For instance, as described above, in some embodiments an acoustic signature can he generated based on a measured twinkling signature of a marker. This acoustic signature can be used to generate an auditory cue (e.g., a sound) that is output to the user and indicates a localization of a marker. Additionally or alternatively, the output may be haptic feedback provided to the user that indicates a proximity to a localized marker.

In some embodiments, communications systems 1126 can include any suitable hardware, firmware, and/or software for communicating information to computing device 1050 (and, in some embodiments, over communication network 1054 and/or any other suitable communication networks). For example, communications systems 1126 can include one or more transceivers, one or more communication chips and/or chip sets, and so on. In a more particular example, communications systems 1126 can include hardware, firmware and/or software that can be used to establish a wired connection using any suitable port and/or communication standard (e.g., VGA, DVI video, USB, RS-232, etc.), Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

In some embodiments, memory 1128 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 1122 to control the one or more ultrasound transducers 1124, and/or receive data from the one or more ultrasound transducers 1124; to images from data; present content (e.g., images, a user interface) using a display; communicate with one or more computing devices 1050; and so on. Memory 1128 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 1128 can include RAM, ROM, EEPROM, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some embodiments, memory 1128 can have encoded thereon, or otherwise stored therein, a program for controlling operation of ultrasound image source 1002. In such embodiments, processor 1122 can execute at least a portion the program to generate images, transmit information and/or content (e.g., data, images) to one or more computing devices 1050, receive information and/or content from one or more computing devices 1050, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone, etc.), and so on.

In some embodiments, any suitable computer readable media can be used for storing instructions for performing the functions and/or processes described herein. For example, in some embodiments, computer readable media can be transitory or non-transitory. For example, non-transitory computer readable media can include media such as magnetic media (e.g., hard disks, floppy disks), optical media (e.g., compact discs, digital video discs, Blu-ray discs), semiconductor media (e.g., random access memory (“RAM”), flash memory, electrically programmable read only memory (“EPROM”), electrically erasable programmable read only memory (“EEPROM”)), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and/or any suitable tangible media. As another example, transitory computer readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and/or any suitable intangible media.

FIG. 12 illustrates an example of an ultrasound system 1200 that can implement the methods described in the present disclosure. The ultrasound system 1200 includes a transducer array 1202 that includes a plurality of separately driven transducer elements 1204. The transducer array 1202 can include any suitable ultrasound transducer array, including linear arrays, curved arrays, phased arrays, and so on. Similarly, the transducer array 1202 can include a 1D transducer, a 1.5D transducer, a 1.75D transducer, a 2D transducer, a 3D transducer, and so on.

When energized by a transmitter 1206, a given transducer element 1204 produces a burst of ultrasonic energy. The ultrasonic energy reflected back to the transducer array 1202 (e.g., an echo) from the object or subject under study is converted to an electrical signal (e.g., an echo signal) by each transducer element 1204 and can be applied separately to a receiver 1208 through a set of switches 1210. The transmitter 1206, receiver 1208, and switches 1210 are operated under the control of a controller 1212, which may include one or more processors. As one example, the controller 1212 can include a computer system.

The transmitter 1206 can be programmed to transmit unfocused or focused ultrasound waves. In some configurations, the transmitter 1206 can also be programmed to transmit diverged waves, spherical waves, cylindrical waves, plane waves, or combinations thereof. Furthermore, the transmitter 1206 can be programmed to transmit spatially or temporally encoded pulses.

The receiver 1208 can be programmed to implement a suitable detection sequence for the imaging task at hand. In some embodiments, the detection sequence can include one or more of line-by-line scanning, compounding plane wave imaging, synthetic aperture imaging, and compounding diverging beam imaging.

In some configurations, the transmitter 1206 and the receiver 1208 can be programmed to implement a high frame rate. For instance, a frame rate associated with an acquisition pulse repetition frequency (“PRF”) of at least 100 Hz can be implemented. In some configurations, the ultrasound system 1200 can sample and store at least one hundred ensembles of echo signals in the temporal direction.

The controller 1212 can be programmed to select and implement an imaging sequence for acquiring ultrasound data. The controller 1212 can also be programmed to control various parameters of the ultrasound system 1200 in order to optimize the visualization of the non-metallic markers described in the present disclosure. For instance, the controller 1212 can be programmed to adjust the color gain, color-write priority, color Doppler frequency, color focus, wall filter, pulse repetition frequency, and other suitable parameters, such as those parameters described above in more detail.

A scan can be performed by setting the switches 1210 to their transmit position, thereby directing the transmitter 1206 to be turned on momentarily to energize transducer elements 1204 during a single transmission event according to the selected imaging sequence. The switches 1210 can then be set to their receive position and the subsequent echo signals produced by the transducer elements 1204 in response to one or more detected echoes are measured and applied to the receiver 1208. The separate echo signals from the transducer elements 1204 can be combined in the receiver 1208 to produce a single echo signal.

The echo signals are communicated to a processing unit 1214, which may be implemented by a hardware processor and memory, to process echo signals or images generated from echo signals. As an example, the processing unit 1214 can generate images that depict twinkling artifacts caused by the non-metallic markers described in the present disclosure. Images produced from the echo signals by the processing unit 1214 can be displayed on a display system 1216.

The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention. 

1. A method for localizing an ultrasound-detectable marker, the method comprising: (a) operating an ultrasound system to select imaging parameters, wherein the imaging parameters are selected to optimize generating a twinkling artifact signature; (b) obtaining Doppler ultrasound data using the ultrasound system operating with the selected imaging parameters, wherein the Doppler ultrasound. data are obtained from a region-of-interest (ROI) containing a marker that when insonated with ultrasound generates a twinkling artifact signature; and (c) localizing the marker in the ROI based on the twinkling artifact signature.
 2. The method of claim 1, wherein the imaging parameters comprise at least one of color ultrasound transmit frequency, color gain, color scale, threshold, and wall filter.
 3. The method of claim 2, wherein the ultrasound system includes a broad-spectrum linear transducer.
 4. The method of claim 3, wherein the imaging parameters comprise: a color scale setting selected from a range of ±2 cm/s to ±12 cm/s; a color ultrasound transmit frequency setting selected from a range of 3.1 MHz to 6.3 MHz; and a color gain setting selected from a range of 18 dB to 25 dB.
 5. The method of claim 4, wherein the color scale setting is selected from a range of ±3 cm/s to ±6 cm/s.
 6. The method of claim 4, wherein the color gain setting is selected from a range of 19.5 dB to 23.5 dB.
 7. The method of claim 3, wherein the imaging parameters comprise: a color scale setting selected from a range of ±2 cm/s to ±12 cm/s; a color ultrasound transmit frequency setting selected from a range of 3.1 MHz to 6.3 MHz; and a color gain setting selected from a range of 40% to 60%.
 8. The method of claim 2, wherein the ultrasound system includes a broad-spectrum linear matrix-array transducer.
 9. The method of claim 8, wherein the imaging parameters comprise: a color scale setting selected from a range of ±3 cm/s to ±9 cm/s; a color ultrasound transmit frequency setting selected from a range of 5.0 MHz to 12.5 MHz; and a color gain setting selected from a range of 18 dB to 25 dB.
 10. The method of claim 9, wherein the color scale setting is selected from a range of ±5 cm/s to ±7 cm/s.
 11. The method of claim 9, wherein the color ultrasound transmit frequency setting is selected from a range of 6 MHz to 7 MHz.
 12. The method of claim 9, wherein the color gain setting is selected from a range of 20.5 dB to 23.5 dB.
 13. The method of claim 8, wherein the imaging parameters comprise: a color scale setting selected from a range of ±3 cm/s to ±9 cm/s; a color ultrasound transmit frequency setting selected from a range of 5.0 MHz to 12.5 MHz; and a color gain setting selected from a range of 40% to 70%.
 14. The method of claim 2, wherein the ultrasound system includes a curvilinear array transducer.
 15. The method of claim 14, wherein the imaging parameters comprise: a color scale setting selected from a range of ±4 cm/s to ±20 cm/s; a color ultrasound transmit frequency setting selected from a range of 2 MHz to 4 MHz; and a color gain setting selected from a range of 14 dB to 25 dB.
 16. The method of claim 15, wherein the color scale setting is selected from a range of ±6 cm/s to ±18 cm/s.
 17. The method of claim 15, wherein the color ultrasound transmit frequency setting is selected from a range of 2.1 MHz to 3.6 MHz.
 18. The method of claim 15, wherein the color gain setting is selected from a range of 14 dB to 23 dB.
 19. The method of claim 14, wherein the imaging parameters comprise: a color scale setting selected from a range of ±4 cm/s to ±20 cm/s; a color ultrasound transmit frequency setting selected from a range of 2 MHz to 4 MHz; and a color gain setting selected from a range of 40% to 70%.
 20. The method of claim 1, wherein the imaging parameters comprise pulse repetition frequency and at least one of color scale and color ultrasound transmit frequency, and wherein the pulse repetition frequency is modulated by the at least one of color scale and color ultrasound transmit frequency.
 21. The method of claim 1, wherein the imaging parameter comprise at least one of focal zone, field-of-view, and color flow region-of-interest.
 22. The method of claim 21, wherein the focal zone is selected to be within a threshold distance from the marker in the ROI.
 23. The method of claim 22, wherein the threshold distance is 1 centimeter.
 24. The method of claim 22, wherein the threshold distance is selected to be a distance posterior to the marker in the ROI.
 25. The method of claim 21, wherein the color flow region-of-interest is selected to have a width equal to one-half of a width of an imaging region.
 26. The method of claim 1, further comprising repeating steps (a) and (b) while varying at least one of the selected imaging parameters and analyzing the Doppler ultrasound data to identify a presence of the twinkling artifact signature in order to select the imaging parameters that optimize the twinkling artifact signature.
 27. The method of claim 1, wherein localizing the marker in the ROI comprises computing a spatiotemporal variation of the twinkling artifact signature in the Doppler ultrasound data and localizing the marker in the ROI based on the spatiotemporal variation of the twinkling artifact signature.
 28. The method of claim 27, further comprising generating an auditory output to a user based on localizing the marker.
 29. The method of claim 27, further comprising generating a haptic feedback signal for a user based on localizing the marker.
 30. The method of claim 1, wherein the marker comprises a metallic biopsy clip that when insonated generates the twinkling artifact signature.
 31. The method of claim 30, wherein the metallic biopsy clip is coated in a non-metallic material.
 32. The method of claim 30, wherein at least part of a surface of the metallic biopsy clip is textured to generate the twinkling artifact signature when insonated.
 33. The method of claim 1, wherein the marker is coupled to a medical instrument and localizing the marker in the ROI comprises localizing the medical instrument.
 34. The method of claim 33, wherein the marker is a coating applied to a surface of the medical instrument.
 35. The method of claim 33, wherein the medical instrument comprises at least one of a clip, a wire, a needle, a brachytherapy needle, a tube, a drain, a catheter, an endoscopic capsule, a cardiac pacer lead, an implant, a suture, and a prosthetic valve.
 36. The method of claim 1, wherein the marker comprises a portion of a medical instrument that has been textured to generate the twinkling artifact signature and localizing the marker in the ROI comprises localizing the medical instrument.
 37. The method of claim 36, wherein the medical instrument comprises at least one of a clip, a wire, a needle, a brachytherapy needle, a tube, a drain, a catheter, an endoscopic capsule, a cardiac pacer lead, an implant, a suture, and a prosthetic valve.
 38. The method of claim 1, wherein the ultrasound system includes a curvilinear array transducer and the marker is at least one of coupled to a medical instrument or a portion of a medical instrument that has been textured to generate the twinkling artifact signature.
 39. The method of claim 38, wherein the medical instrument is a brachytherapy needle.
 40. The method of claim 1, wherein the Doppler ultrasound data comprise non-gated acoustic signal data. 